Sitosterolemia-10 years observation in two sisters

Abstract

Familial hypercholesterolemia due to heterozygous low-density lipoprotein-receptor mutations is a common inborn errors of metabolism. Secondary hypercholesterolemia due to a defect in phytosterol metabolism is far less common and may escape diagnosis during the work-up of patients with dyslipidemias. Here we report on two sisters with the rare, autosomal recessive condition, sitosterolemia. This disease is caused by mutations in a defective adenosine triphosphate-binding cassette sterol excretion transporter, leading to highly elevated plant sterol concentrations in tissues and to a wide range of symptoms. After a delayed diagnosis, treatment with a diet low in plant lipids plus ezetimibe to block the absorption of sterols corrected most of the clinical and biochemical signs of the disease. We followed the two patients for over 10 years and report their initial presentation and long-term response to treatment.

Keywords: ABCG5 or the ABCG8 gene; familial hypercholesterolemia; phytosterols; sitosterolemia; xanthoma.

Figure 1

Model for absorption and secretion of cholesterol and plant sterols: Physiologically, the ABCG5/G8 transporter pumps absorbed nutrition sterols (absorbed through the Niemann‐Pick‐C1‐like 1, short NPC1L1) back into the intestinal lumen or into the bile, with a preference for non‐cholesterol sterols, if they are present. It occurs in the apical membrane of small intestine enterocytes and hepatocytes. BA, bile acids; PL, phospholipids; BSEP, bile salt export pump; BDR3, multiple drug resistance protein 3; NTCP, sodium/taurocholate co‐transporter; SR‐B1, scavenger‐receptor B1 (HDL‐receptor)

Figure 2

Lipid levels, symptoms, and treatments of both patients during the observation period

Figure 3

Clinical pictures and CT scan of patient 1. Xanthelasma at age 11.2 (A), 11.9 (B), and 13.3 years (C). Xanthomata at age 8.8 (D), 11.2 (E), and 13.3 years (F). CT scan with cardiac calcifications at age 13.5, arrows indicate site of calcifications (G, H). CT, computed tomography